PT - JOURNAL ARTICLE AU - Nathalie Acevedo AU - Lovisa Reinius AU - Anna Gref AU - Erik Melen AU - Annika Sääf AU - Göran Pershagen AU - Annika Scheynius AU - Juha Kere AU - Cilla Söderhäll TI - Analyses of genetic association and DNA methylation in the ORMDL3/GSDMB locus DP - 2013 Sep 01 TA - European Respiratory Journal PG - 1527 VI - 42 IP - Suppl 57 4099 - http://erj.ersjournals.com/content/42/Suppl_57/1527.short 4100 - http://erj.ersjournals.com/content/42/Suppl_57/1527.full SO - Eur Respir J2013 Sep 01; 42 AB - Background: Several independent studies have replicated the genetic association between polymorphisms in ORMDL3 and GSDMB and the risk of childhood asthma. The causal mechanisms remain unknown but there is evidence suggesting that epigenetic alterations, e.g. DNA methylation, might contribute. We aim to analyze the methylation status of the genes GSDMB/ORMDL3 and the risk of asthma.Methods: We genotyped 17 SNPs in GSDMB and ORMDL3 in the Swedish birth cohort (BAMSE, n =2033) including the GWAS hits rs2305480 and rs7216389. DNA methylation levels at 20 CpG sites were quantified in whole blood in the 17q12-21 region by EpiTYPER or pyrosequencing in a subset of the BAMSE study (n=261).Results and conclusions: We confirmed the genetic association between the 17q12-21 region and physician-diagnosed asthma and wheezing. No association was seen to rhinitis, atopic sensitization, or allergic or non-allergic asthma after correction for multiple testing. Our analyses show that the CpG sites in GSDMB are in general highly methylated, and no differences were seen in methylation levels between asthmatic children and controls in 10 non-polymorphic CpG sites analyzed in GSDMB . However, in ORMDL3 DNA methylation levels in two CpG sites were significantly lower in asthmatic children compared to healthy controls.